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Crohn Disease: HELP
Articles by C. W. Lees
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, C. W. Lees wrote the following 11 articles about Crohn Disease.
 
+ Citations + Abstracts
1 Review Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis. 2016

Kennedy, N A / Warner, B / Johnston, E L / Flanders, L / Hendy, P / Ding, N S / Harris, R / Fadra, A S / Basquill, C / Lamb, C A / Cameron, F L / Murray, C D / Parkes, M / Gooding, I / Ahmad, T / Gaya, D R / Mann, S / Lindsay, J O / Gordon, J / Satsangi, J / Hart, A / McCartney, S / Irving, P / Anonymous5810858 / Lees, C W. ·Edinburgh, UK. · London, UK. · Winchester, UK. · Newcastle Upon Tyne, UK. · Glasgow, UK. · Cambridge, UK. · Colchester, UK. · Exeter, UK. ·Aliment Pharmacol Ther · Pubmed #26892328.

ABSTRACT: BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 10 CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

2 Review Systematic review: The use of thiopurines or anti-TNF in post-operative Crohn's disease maintenance--progress and prospects. 2014

Jones, G R / Kennedy, N A / Lees, C W / Arnott, I D / Satsangi, J. ·Department of Gastroenterology, Western General Hospital, Edinburgh, UK. ·Aliment Pharmacol Ther · Pubmed #24738574.

ABSTRACT: BACKGROUND: Post-operative recurrence of Crohn's disease is an important management challenge, with 2-year recurrence rates defined by clinical, endoscopic and radiological parameters of up to 77%, 64% and 49%. Clinical and severe endoscopic recurrence vary widely in controlled trials from 13% to 36% and 22% to 56% with thiopurine treatment or 0% and 9% with infliximab treatment respectively at 1 year. AIMS: To provide a review of the evidence for thiopurine or anti-TNF use in post-operative Crohn's disease, and to assess the ability to identify those patients at highest risk of recurrent disease. METHODS: A literature search was undertaken using Medline, Embase and Cochrane databases to identify studies using search terms 'thiopurine', 'azathioprine', 'mercaptopurine', 'Infliximab', 'adalimumab', 'Anti-TNF', 'Crohn's disease', 'post-operative' and 'recurrence'. RESULTS: Trials to examine this important area have proved difficult to execute, with recruitment and retention of patients posing major challenges to randomised clinical trials. There have been four RCTs of 433 patients of thiopurine therapy (with three meta-analyses of these data), and one of anti-TNF therapy involving 24 patients. Overall the efficacy data for thiopurine use in this setting are inconclusive, and other than smoking, there are no consistent predictors of post-operative relapse. CONCLUSIONS: At present, evidence for routine use of thiopurine treatment in post-operative Crohn's disease is heterogeneous and unconvincing. Stratification by risk of relapse emerges as a key challenge in post-operative management that needs to be addressed, using clinical parameters and emerging biomarkers. The evidence for prophylactic anti-TNF use is limited though promising, with its routine use guided by early assessment of relapse.

3 Review A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis. 2013

Kennedy, N A / Rhatigan, E / Arnott, I D R / Noble, C L / Shand, A G / Satsangi, J / Lees, C W. ·Gastrointestinal Unit, Western General Hospital, Edinburgh, UK; Gastrointestinal research, Centre for molecular medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK. ·Aliment Pharmacol Ther · Pubmed #24117596.

ABSTRACT: BACKGROUND: Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals. AIMS: To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets. METHODS: A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies). RESULTS: Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine. CONCLUSIONS: This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.

4 Review New IBD genetics: common pathways with other diseases. 2011

Lees, C W / Barrett, J C / Parkes, M / Satsangi, J. ·Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK. charlie.lees@ed.ac.uk ·Gut · Pubmed #21300624.

ABSTRACT: Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility loci/genes (71 Crohn's disease; 47 ulcerative colitis) to date. Approximately one-third of loci described confer susceptibility to both Crohn's disease and ulcerative colitis. Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. The evolving genetic architecture of IBD has furthered our understanding of disease pathogenesis. For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). However, when the data are analysed in more detail, deeper themes emerge including the shared susceptibility seen with other diseases. Many immune-mediated diseases overlap in this respect, paralleling the reported epidemiological evidence. However, in several cases the reported shared susceptibility appears at odds with the clinical picture. Examples include both type 1 and type 2 diabetes mellitus. In this review we will detail the presently available data on the genetic overlap between IBD and other diseases. The discussion will be informed by the epidemiological data in the published literature and the implications for pathogenesis and therapy will be outlined. This arena will move forwards very quickly in the next few years. Ultimately, we anticipate that these genetic insights will transform the landscape of common complex diseases such as IBD.

5 Article Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort. 2019

Plevris, N / Chuah, C S / Allen, R M / Arnott, I D / Brennan, P N / Chaudhary, S / Churchhouse, A M D / Din, S / Donoghue, E / Gaya, D R / Groome, M / Jafferbhoy, H M / Jenkinson, P W / Lam, W L / Lyons, M / Macdonald, J C / MacMaster, M / Mowat, C / Naismith, G D / Potts, L F / Saffouri, E / Seenan, J P / Sengupta, A / Shasi, P / Sutherland, D I / Todd, J A / Veryan, J / Watson, A J M / Watts, D A / Jones, G R / Lees, C W. ·The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK. · Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK. · Department of Gastroenterology, Ninewells Hospital, Dundee, UK. · Department of Gastroenterology, University Hospital Hairmyres, East Kilbride, UK. · Department of Gastroenterology, Victoria Hospital, Kirkcaldy, UK. · Department of Gastroenterology, Forth Valley Royal Hospital, Larbert, UK. · Department of Colorectal Surgery, Raigmore Hospital, Inverness, UK. · Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow, UK. · Department of Gastroenterology, Royal Alexandra Hospital, Paisley, UK. · Department of Gastroenterology, Raigmore Hospital, Inverness, UK. ·J Crohns Colitis · Pubmed #30768123.

ABSTRACT: BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

6 Article Faecal Calprotectin and Magnetic Resonance Enterography in Ileal Crohn's Disease: Correlations Between Disease Activity and Long-Term Follow-Up. 2019

Jones, G R / Fascì-Spurio, F / Kennedy, N A / Plevris, N / Jenkinson, P / Lyons, M / Wong, L / MacLean, P / Glancy, S / Lees, C W. ·Western General Hospital, Gastrointestinal Unit, Edinburgh, UK. · University of Edinburgh, Gastrointestinal Unit, Centre for Genomic and Experimental Medicine, Edinburgh, UK. · Sapienza University, Gastroenterology Unit, Rome, Italy. · Western General Hospital, Department of Radiology, Edinburgh, UK. ·J Crohns Colitis · Pubmed #30452618.

ABSTRACT: BACKGROUND AND AIMS: Magnetic resonance enterography [MRE] is the gold standard for assessing ileal inflammation in Crohn's disease [CD]. The aim of the present study was to correlate faecal calprotectin [FC] to MRE via a simple score in an exclusive ileal cohort with long-term follow-up for association with time to surgery or biologic therapy. METHODS: In total, 150 MRE studies with matched FC [±30 days] were identified from the Edinburgh FC Register [2008-12; n = 18138]. Scans were re-read blinded to clinical data, independently, by two expert gastrointestinal radiologists, to generate a simple MRE score [range 0-10] from assessment of the worst intestinal segment plus total disease extent. RESULTS: In total, 119 MRE scans were evaluated from 104 patients with ileal CD [L1 or L3 with panproctocolectomy]. Receiver operating characteristic analysis showed an area under the curve of 0.77 [0.67-0.87, p < 0.0001] for FC and MRE score >1, with an optimal cut-off of 145 μg/g for severe inflammation on MRE with 69.3% [57.6-79.5] sensitivity and 71.4% [53.7-85.4] specificity. Long-term follow-up over a median [interquartile range] of 2086 days [1786-2353] revealed FC ≥ 145 μg/g was associated with reduced biologic-free survival until 3 years following MRE, whereas MRE score [severe vs absent] was associated with reduced surgery- and biologic-free survival throughout follow-up. Backwards stepwise logistic regression revealed that length of ileal disease (odds ratio [OR] 3.8, 1.1-13.2, p = 0.034) and increased bowel wall thickness at MRE [OR 4.2, 1.6-10.7, p < 0.0001] or female sex [OR 5.2, 1.5-18.7, p = 0.011] increased the risk of biologic use or surgery, respectively. CONCLUSIONS: FC correlates well with MRE assessment of ileal CD with MRE parameters associated with long-term biologic- and surgery-free remission.

7 Article Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients. 2014

Kennedy, N A / Kalla, R / Warner, B / Gambles, C J / Musy, R / Reynolds, S / Dattani, R / Nayee, H / Felwick, R / Harris, R / Marriott, S / Senanayake, S M / Lamb, C A / Al-Hilou, H / Gaya, D R / Irving, P M / Mansfield, J / Parkes, M / Ahmad, T / Cummings, J R F / Arnott, I D / Satsangi, J / Lobo, A J / Smith, M / Lindsay, J O / Lees, C W. ·Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. ·Aliment Pharmacol Ther · Pubmed #25284134.

ABSTRACT: BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

8 Article Multiple sclerosis in the context of TNF blockade and inflammatory bowel disease. 2014

Hare, N C / Hunt, D P J / Venugopal, K / Ho, G-T / Beez, T / Lees, C W / Gibson, R / Weller, B / Satsangi, J. ·Department of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. david_hunt200@hotmail.com. ·QJM · Pubmed #22240391.

ABSTRACT: -- No abstract --

9 Article Sarcoidosis complicating treatment with natalizumab for Crohn's disease. 2011

Parisinos, C A / Lees, C W / Wallace, W A H / Satsangi, J. ·Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. j.satsangi@ed.ac.uk. ·Thorax · Pubmed #21233484.

ABSTRACT: Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.

10 Minor Letter: faecal calprotectin and lactoferrin - accurate biomarkers in post-operative Crohn's disease - authors' reply. Letter: biologic therapies are effective for prevention of post-operative Crohn's disease recurrence - authors' reply. 2014

Jones, G R / Kennedy, N A / Lees, C W / Arnott, I D / Satsangi, J. ·Department of Gastroenterology, Western General Hospital, Edinburgh, UK. gareth.jones@ed.ac.uk. ·Aliment Pharmacol Ther · Pubmed #25040750.

ABSTRACT: -- No abstract --

11 Minor Letter: Azathioprine-induced pancreatitis and subsequent tolerance of mercaptopurine--authors' reply. 2014

Kennedy, N A / Lees, C W. ·Gastrointestinal Unit, Western General Hospital, Edinburgh, UK; Gastrointestinal research, Centre for molecular medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK. ·Aliment Pharmacol Ther · Pubmed #24447316.

ABSTRACT: -- No abstract --